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Sildenafil Improves the Beneficial Haemodynamic Effects of Intravenous Nitrite Infusion during Acute Pulmonary Embolism
Author(s) -
DiasJunior Carlos A.,
Montenegro Marcelo F.,
Florencio Barbara C.,
TanusSantos Jose E.
Publication year - 2008
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2008.00299.x
Subject(s) - sildenafil , medicine , anesthesia , nitric oxide , nitrite , cyclic guanosine monophosphate , pulmonary artery , vascular resistance , pulmonary embolism , saline , pulmonary hypertension , hemodynamics , cgmp specific phosphodiesterase type 5 , pharmacology , chemistry , nitrate , organic chemistry
Acute pulmonary embolism produces acute pulmonary hypertension, which can be counteracted by activating the nitric oxide–cyclic guanosine 3′,5′‐monophosphate (cGMP) pathway. While previous studies have shown that sildenafil (an inhibitor of cGMP‐specific phosphodiesterase type 5) or nitrite (a storage molecule for nitric oxide) produces beneficial effects during acute pulmonary embolism, no previous study has examined whether the combination of these drugs can produce additive effects. Here, we expand previous findings and examine whether sildenafil enhances the beneficial haemodynamic effects produced by a low‐dose infusion of nitrite in a dog model of acute pulmonary embolism. Haemodynamic and arterial blood gas evaluations were performed in non‐embolized dogs treated with saline (n = 4), and in embolized dogs (intravenous injections of microspheres) that received nitrite (6.75 µmol/kg intravenously over 15 min. followed by 0.28 µmol/kg/min.) and sildenafil (0.25 mg/kg over 30 min.; n = 8), or nitrite followed by saline (n = 8), or saline followed by sildenafil (n = 7), or only saline (n = 8). Plasma thiobarbituric acid‐reactive substances (TBARS) concentrations were determined using a fluorometric method. Acute pulmonary embolism increased pulmonary artery pressure by ∼24 mmHg. While the infusion of nitrite or sildenafil infusions reversed this increase by ∼42% (both P < 0.05), the combined infusion of both drugs reversed this increase by ∼58% (P < 0.05). Similar effects were seen on the pulmonary vascular resistance index. Nitrite or sildenafil alone produced no significant hypotension. However, the combined infusion of both drugs caused transient hypotension (P < 0.05). Both dugs, either alone or combined, blunted the increase in TBARS concentrations caused by acute pulmonary embolism (all P < 0.05). These results suggest that sildenafil improves the beneficial haemodynamic effects of nitrite during acute pulmonary embolism.